Citations

AbstractINTRODUCTIONWe used sex and apolipoprotein E ε4 (APOE ε4) carrier status as predictors of pathologic burden in early‐onset Alzheimer's disease (EOAD).METHODSWe included baseline data from 77 cognitively normal (CN), 230 EOAD, and 70 EO non‐Alzheimer's disease (EOnonAD) participants from the Longitudinal Early‐Onset Alzheimer's Disease Study (LEADS). We stratified each diagnostic group by males and females, then further subdivided each sex by APOE ε4 carrier status and compared imaging biomarkers in each stratification. Voxel‐wise multiple linear regressions yielded statistical brain maps of gray matter density, amyloid, and tau PET burden.RESULTSEOAD females had greater amyloid and tau PET burdens than males. EOAD female APOE ε4 non‐carriers had greater amyloid PET burdens and greater gray matter atrophy than female ε4 carriers. EOnonAD female ε4 non‐carriers also had greater gray matter atrophy than female ε4 carriers.DISCUSSIONThe effects of sex and APOE ε4 must be considered when studying these populations.HIGHLIGHTS Novel analysis examining the effects of biological sex and apolipoprotein E ε4 (APOE ε4) carrier status on neuroimaging biomarkers among early‐onset Alzheimer's disease (EOAD), early‐onset non‐AD (EOnonAD), and cognitively normal (CN) participants. Female sex is associated with greater pathology burden in the EOAD cohort compared to male sex. The effect of APOE ε4 carrier status on pathology burden was the most impactful in females across all cohorts.

Abstract INTRODUCTION We compared white matter hyperintensities (WMHs) in early‐onset Alzheimer's disease (EOAD) with cognitively normal (CN) and early‐onset amyloid‐negative cognitively impaired (EOnonAD) groups in the Longitudinal Early‐Onset Alzheimer's Disease Study. METHODS We investigated the role of increased WMH in cognition and amyloid and tau burden. We compared WMH burden of 205 EOAD, 68 EOnonAD, and 89 CN participants in lobar regions using t ‐tests and analyses of covariance. Linear regression analyses were used to investigate the association between WMH and cognitive impairment and that between amyloid and tau burden. RESULTS EOAD showed greater WMHs compared with CN and EOnonAD participants across all regions with no significant differences between CN and EOnonAD groups. Greater WMHs were associated with worse cognition. Tau burden was positively associated with WMH burden in the EOAD group. DISCUSSION EOAD consistently showed higher WMH volumes. Overall, greater WMHs were associated with worse cognition and higher tau burden in EOAD. Highlights This study represents a comprehensive characterization of WMHs in sporadic EOAD. WMH volumes are associated with tau burden from positron emission tomography (PET) in EOAD, suggesting WMHs are correlated with increasing burden of AD. Greater WMH volumes are associated with worse performance on global cognitive tests. EOAD participants have higher WMH volumes compared with CN and early‐onset amyloid‐negative cognitively impaired (EOnonAD) groups across all brain regions.

AbstractIntroductionOne goal of the Longitudinal Early Onset Alzheimer's Disease Study (LEADS) is to define the fluid biomarker characteristics of early‐onset Alzheimer's disease (EOAD).MethodsCerebrospinal fluid (CSF) concentrations of Aβ1‐40, Aβ1‐42, total tau (tTau), pTau181, VILIP‐1, SNAP‐25, neurogranin (Ng), neurofilament light chain (NfL), and YKL‐40 were measured by immunoassay in 165 LEADS participants. The associations of biomarker concentrations with diagnostic group and standard cognitive tests were evaluated.ResultsBiomarkers were correlated with one another. Levels of CSF Aβ42/40, pTau181, tTau, SNAP‐25, and Ng in EOAD differed significantly from cognitively normal and early‐onset non‐AD dementia; NfL, YKL‐40, and VILIP‐1 did not. Across groups, all biomarkers except SNAP‐25 were correlated with cognition. Within the EOAD group, Aβ42/40, NfL, Ng, and SNAP‐25 were correlated with at least one cognitive measure.DiscussionThis study provides a comprehensive analysis of CSF biomarkers in sporadic EOAD that can inform EOAD clinical trial design.

AbstractIntroductionWe examined neuropsychiatric symptoms (NPS) and psychotropic medication use in a large sample of individuals with early‐onset Alzheimer's disease (EOAD; onset 40‐64 years) at the midway point of data collection for the Longitudinal Early‐onset Alzheimer's Disease Study (LEADS).MethodsBaseline NPS (Neuropsychiatric Inventory – Questionnaire; Geriatric Depression Scale) and psychotropic medication use from 282 participants enrolled in LEADS were compared across diagnostic groups – amyloid‐positive EOAD (n = 212) and amyloid negative early‐onset non‐Alzheimer's disease (EOnonAD; n = 70).ResultsAffective behaviors were the most common NPS in EOAD at similar frequencies to EOnonAD. Tension and impulse control behaviors were more common in EOnonAD. A minority of participants were using psychotropic medications, and use was higher in EOnonAD.DiscussionOverall NPS burden and psychotropic medication use were higher in EOnonAD than EOAD participants. Future research will investigate moderators and etiological drivers of NPS, and NPS differences in EOAD versus late‐onset AD.

AbstractObjectiveThe Longitudinal Early‐Onset Alzheimer's Disease Study (LEADS) seeks to provide comprehensive understanding of early‐onset Alzheimer's disease (EOAD; onset <65 years), with the current study profiling baseline clinical, cognitive, biomarker, and genetic characteristics of the cohort nearing the data‐collection mid‐point.MethodsData from 371 LEADS participants were compared based on diagnostic group classification (cognitively normal [n = 89], amyloid‐positive EOAD [n = 212], and amyloid‐negative early‐onset non‐Alzheimer's disease [EOnonAD; n = 70]).ResultsCognitive performance was worse for EOAD than other groups, and EOAD participants were apolipoprotein E (APOE) ε4 homozygotes at higher rates. An amnestic presentation was common among impaired participants (81%), with several clinical phenotypes present. LEADS participants generally consented at high rates to optional trial procedures.ConclusionsWe present the most comprehensive baseline characterization of sporadic EOAD in the United States to date. EOAD presents with widespread cognitive impairment within and across clinical phenotypes, with differences in APOE ε4 allele carrier status appearing to be relevant.HIGHLIGHTS Findings represent the most comprehensive baseline characterization of sporadic early‐onset Alzheimer's disease (EOAD) to date. Cognitive impairment was widespread for EOAD participants and more severe than other groups. EOAD participants were homozygous apolipoprotein E (APOE) ε4 carriers at higher rates than the EOnonAD group. Amnestic presentation predominated in EOAD and EOnonAD participants, but other clinical phenotypes were present.

AbstractOBJECTIVEInvestigation of learning slopes in early‐onset dementias has been limited. The current study aimed to highlight the sensitivity of learning slopes to discriminate disease severity in cognitively normal participants and those diagnosed with early‐onset dementia with and without β‐amyloid positivityMETHODData from 310 participants in the Longitudinal Early‐Onset Alzheimer's Disease Study (aged 41 to 65) were used to calculate learning slope metrics. Learning slopes among diagnostic groups were compared, and the relationships of slopes with standard memory measures were determinedRESULTSWorse learning slopes were associated with more severe disease states, even after controlling for demographics, total learning, and cognitive severity. A particular metric—the learning ratio (LR)—outperformed other learning slope calculations across analysesCONCLUSIONSLearning slopes appear to be sensitive to early‐onset dementias, even when controlling for the effect of total learning and cognitive severity. The LR may be the learning measure of choice for such analyses.Highlights Learning is impaired in amyloid‐positive EOAD, beyond cognitive severity scores alone. Amyloid‐positive EOAD participants perform worse on learning slopes than amyloid‐negative participants. Learning ratio appears to be the learning metric of choice for EOAD participants.

Abstract Carotid artery angioplasty and stenting (CAS) has been shown to be equally effective as carotid endarterectomy (CEA) for carotid stenosis in both symptomatic and asymptomatic disease. 1 In patients who are considered high risk for endarterectomy, CAS is safe and effective. 2 While this is a common procedure, proper technique is crucial to ensure that the procedure is safe with minimal risk of stroke. This patient consented to treatment. The following is a video detailing the CAS procedure in a 77-yr-old male with a symptomatic 65% carotid stenosis (by NASCET criteria 3 ) in a patient with prior CEA.

Abstract Since the International Subarachnoid Aneurysm Trial, 1 endovascular treatment has been the favored treatment for appropriate ruptured intracranial aneurysms. While our endovascular technology has advanced to allow us to treat the majority of intracranial aneurysms, simple coil embolization is still the most common modality. This video demonstrates the fundamentals of aneurysm catheterization and coiling for safe treatment. In addition, the set-up and devices are detailed. This video is to add to the library of basic techniques that will aid a large number of practitioners. This patient consented to endovascular treatment. The video demonstrates endovascular coil embolization of a posterior communicating artery aneurysm in a 76-yr-old female who presented with a subarachnoid hemorrhage. Image of biplane suite in video used courtesy of Siemens Medical Solutions USA, Inc. Illustration at 5:12 reprinted from Yasargil MG, et al, Microneurosurgery IV B , p. 9, Thieme, New York, 1995.

Abstract Acute carotid terminus occlusion (CTO) is responsible for up to 5% of acute ischemic strokes secondary to emergent large vessel occlusion (ELVO) and up to 20% of acute internal carotid artery (ICA) occlusions. 1 The term “CTO” has also been used to describe occlusions in the supra-clinoid segment or at the bifurcation of the ICA. Compared to other ELVOs, patients with CTO present with higher stroke severity and larger infarct volume, likely to be a result of disruption of direct Circle of Willis collaterals across the anterior communicating artery (AComA) and posterior communicating artery (PComA). 2,3 Similary, CTO is usually associated with worse prognosis compared to other ELVOs in general. With regard to response to treatment, previous studies have reported significantly lower recanalization rates with intravenous alteplase with CTO compared to M1 segment occlusion. With regard to the safety and efficacy of mechanical thrombectomy, prior reports provide conflicting results with some reporting lower successful recanalization rates with CTO compared to M1 occlusion, and others reporting similar results. In our experience, we have found that successful recanalization of CTO can be achieved with a similar approach to M1 occlusions utilizing a direct aspiration first pass technique (ADAPT). 3,4 Herein, we present a case of CTO for which we performed mechanical thrombectomy using ADAPT. This procedure was an emergent standard of care procedure for which a consent was not required and so not obtained.

Background and Purpose: Based on promising results of the Solitaire FR With the Intention for Thrombectomy (SWIFT) trial, Solitaire FR stent retriever device recently received the Food and Drug Administration (FDA) approval for recanalization of cerebral vessels in patients with acute ischemic stroke. Real world experience with this device since its FDA approval in the United States has not been previously described. Methods: We conducted retrospective analysis of consecutive acute ischemic strokes cases from March 2012 to July 2012 in 10 centers within the United States, where Solitaire FR was used as a single device or in conjunction with other intra-arterial endovascular approaches. Results: A total of 107 patients were identified (mean age, 64 years; male gender, 51%; mean admission NIHSS score 17). Mean time from symptom onset to angiogram (groin puncture) was 4 hrs 47 min. Intravenous thrombolysis with tissue plasminogen activator (tPA) was administered in 37% of cases. Other endovascular techniques utilized in conjunction with Solitaire FR included intra-arterial thrombolysis with tPA (12% of patients), aspiration thrombectomy with Penumbra system (29%) and stenting (17%). Complete recanalization (TIMI 2-3) was achieved in 88% of patients. The rate of sICH within the first 24 hours was 15%. In-hospital mortality was 24%. 30-day clinical follow up data was available on 82 (77%) patients. Of those, 28 patients (34%) had favorable functional outcome (defined as modified Ranking Scale,mRS≤2) and 22 patients (27%) had excellent functional outcome (mRS≤1) at 30 days. Three or more passes with the Solitaire device was associated with a higher incidence of mortality compared with patients requiring 1 or 2 passes only (43% and 18% respectively, p = 0.011). No statistically significant correlation between clot location or length and outcome was evident. Use of other devices with the Solitaire FR was correlated with worsened outcome (p=0.037). Conclusions: This is the first study describing real-world experience with Solitaire FR device outside the SWIFT trial in the United States. Out study shows that variety of other endovascular approaches are used in conjunction with Solitaire FR.